Kim Yong-Hoon, Noh Jung-Ran, Hwang Jung Hwan, Kim Kyoung-Shim, Choi Dong-Hee, An Jin-Pyo, Oh Won-Keun, Lee Chul-Ho
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Republic of Korea.
Exp Ther Med. 2017 Dec;14(6):5863-5870. doi: 10.3892/etm.2017.5271. Epub 2017 Oct 10.
(SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor α () and interleukin-6 () were significantly decreased in the aorta of SA administered apoE mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction , and in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis.
刺萼龙葵(SA)是一种原产于美国东北部的夏季一年生藤本植物,是一种广泛分布的有害入侵植物。然而,此前尚未对SA的临床应用进行过研究。本研究的目的是确定SA对动脉粥样硬化的影响及其潜在机制。通过给载脂蛋白E缺陷(apoE)小鼠喂食致动脉粥样硬化饮食8周来诱导动脉粥样硬化。在动脉粥样硬化诱导期间,每天通过口服灌胃给予SA。与载体处理的小鼠相比,用SA处理的apoE小鼠在整个主动脉和主动脉窦中的动脉粥样硬化斑块面积显著减少。血浆脂质谱,包括甘油三酯、总胆固醇、高密度脂蛋白和低密度脂蛋白,不受SA给药的影响。值得注意的是,在给予SA的apoE小鼠的主动脉中,包括肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)在内的促动脉粥样硬化细胞因子的基因表达水平显著降低。在脂多糖刺激的RAW 264.7巨噬细胞中,SA也以剂量依赖的方式抑制TNF-α、IL-6和单核细胞趋化蛋白-1(MCP-1)的诱导。此外,在用SA处理的apoE小鼠的主动脉中,包括血管细胞粘附蛋白1(VCAM-1)和细胞间粘附分子1(ICAM-1)在内的内皮细胞粘附分子的基因表达水平降低,随后主动脉中单核细胞/巨噬细胞的浸润减少。总之,据我们所知,这是第一项证明SA能够通过抑制致动脉粥样硬化饮食喂养的apoE小鼠主动脉中促炎因子的表达来抑制动脉粥样硬化发展的研究。本研究可能为将环境问题杂草SA作为预防动脉粥样硬化的治疗有效天然产物的应用提供新的见解。